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This paper presents the modeling, design, fabrication and testing of monolithic electrostatic curved-electrode zipping actuators fabricated by deep reactive ion etching (DRIE). In contrast to traditional curved-electrode zipping actuators, the design of the actuators presented here utilizes a compliant starting cantilever to significantly reduce the initial pull-in voltage by closing the gap (kerf) generated by DRIE. Thus, the actuators achieve high actuation force at a relatively low voltage. For example, two actuators each with dimensions of 4.5 mm * 100 µm * 300 µm are used to drive a bistable MEMS relay. Together, the two actuators provide up to 10 mN of force over their 80 µm stroke at 140 V. Measurements of the force-displacement relation of these actuators confirm theoretical expectations based both on numerical and analytical methods. Finite element analysis is employed to predict the behavior of the complete bistable relay system. [ABSTRACT FROM AUTHOR]

Abstract: We report the case of a 35-year-old man who had a transient ischemic cerebral attack and then underwent a percutaneous closure of the patent foramen ovale (PFO) with a Cardiastar device. One year later, the patient developed a cardiac tamponade due to an important hemorrhagic pericardial effusion. Transoesophageal echocardiography showed that one of the struts had impinged on the aortic root in the region adjacent to the transverse pericardial sinus. Therefore, we speculated that the strut had passed through the aortic wall by slow erosion, leading to the pericardial effusion. Cardiac CT and subsequent surgery confirmed the perforation of the left atrial roof and the aortic root by two struts of the device. This is the first reported case of late cardiac tamponade and underscores the importance of long-term follow-up after PFO closure device implantation. [Copyright &y& Elsevier]

Gap junctions, formed by the connexin (Cx) protein family, are intercellular channels that permit the cytoplasmic exchange of ions and small metabolites between neighboring cells, a process called gap junction intercellular communication (GJIC). These channels possess unique properties, including distinctive permeabilities for various signaling molecules, which depend on the connexin member(s) that form them. Importantly, GJIC must be properly controlled as its misregulation might contribute to diseases. Morphological and functional studies have revealed ‘gap junction-like’ structures and cell-to-cell communication involving cells of the immune system. The connexins involved in such contacts have been partially identified in recent years. This review focuses on the potential physiological roles of gap junctions in the development and recruitment of leukocytes as well as in the regulation of the immune response. Furthermore, the importance of GJIC in immuno-inflammatory pathologies is illustrated in atherosclerosis. [Copyright &y& Elsevier]

Magnetic resonance fingerprinting (MRF) is a quantitative MRI (qMRI) framework that provides simultaneous estimates of multiple relaxation parameters as well as metrics of field inhomogeneity in a single acquisition. However, current challenges exist in the forms of (1) scan time; (2) need for custom image reconstruction; (3) large dictionary sizes; (4) long dictionary-matching time. This study aims to introduce a novel streamlined magnetic-resonance fingerprinting (sMRF) framework based on a single-shot echo-planar imaging (EPI) sequence to simultaneously estimate tissue T1, T2, and T2* with integrated B1+ correction. Encouraged by recent work on EPI-based MRF, we developed a method that combines spin-echo EPI with gradient-echo EPI to achieve T2 in addition to T1 and T2* quantification. To this design, we add simultaneous multi-slice (SMS) acceleration to enable full-brain coverage in a few minutes. Moreover, in the parameter-estimation step, we use deep learning to train a deep neural network (DNN) to accelerate the estimation process by orders of magnitude. Notably, due to the high image quality of the EPI scans, the training process can rely simply on Bloch-simulated data. The DNN also removes the need for storing large dictionaries. Phantom scans along with in-vivo multi-slice scans from seven healthy volunteers were acquired with resolutions of 1.1×1.1×3 mm3 and 1.7×1.7×3 mm3, and the results were validated against ground truth measurements. Excellent correspondence was found between our T1, T2, and T2* estimates and results obtained from standard approaches. In the phantom scan, a strong linear relationship (R = 1–1.04, R2>0.96) was found for all parameter estimates, with a particularly high agreement for T2 estimation (R2>0.99). Similar findings are reported for the in-vivo human data for all of our parameter estimates. Incorporation of DNN results in a reduction of parameter estimation time on the order of 1000 x and a reduction in storage requirements on the order of 2500 x while achieving highly similar results as conventional dictionary matching (%differences of 7.4 ± 0.4%, 3.6 ± 0.3% and 6.0 ± 0.4% error in T1, T2, and T2* estimation). Thus, sMRF has the potential to be the method of choice for future MRF studies by providing ease of implementation, fast whole-brain coverage, and ultra-fast T1/T2/T2* estimation. [ABSTRACT FROM AUTHOR]

The prevalence of and outcomes associated with different antithrombotic strategies after left atrial appendage occlusion (LAAO) are not well described. This study sought to evaluate patterns of antithrombotic medication strategies at discharge following LAAO with the Watchman FLX device in real-world practice and to compare the risk of adverse events among the different antithrombotic regimens. The authors evaluated patients in the NCDR (National Cardiovascular Data Registry) LAAO Registry who underwent LAAO with the second-generation LAA closure device between 2020 and 2022. They grouped patients by mutually exclusive discharge antithrombotic strategies and compared the rates of adverse events at 45 days and 6 months using multivariable Cox proportional hazards regression. Among 53,878 patients undergoing successful LAAO with the second-generation LAA closure device, the most common antithrombotic discharge regimens were direct oral anticoagulant (DOAC) plus aspirin (48.3%), DOAC alone (22.6%), dual antiplatelet therapy (8.1%), warfarin plus aspirin (7.7%), and DOAC plus P2Y 12 inhibitor (4.9%). In multivariate analysis, DOAC alone had a lower rate of major adverse events and major bleeding at 45 days of follow-up compared with DOAC plus aspirin (major adverse events: HR: 0.78; 95% CI: 0.68-0.91; major bleeding: HR: 0.69; 95% CI: 0.60-0.80). These differences persisted at 6 months. Warfarin without aspirin also showed lower rates of major bleeding at both time points. No differences were seen in stroke/transient ischemic attack or device-related thrombus. In real-world U.S. practice, discharge on DOAC alone or warfarin alone was associated with a lower rate of adverse events compared with DOAC plus aspirin. [ABSTRACT FROM AUTHOR]

Highlights • rs-fMRI benefits enormously from sampling above the cardiac cycle Nyquist frequency. • Broadening the spectral width significantly improves SNS and TRT for rs-fMRI data. • Filtering the cardiac and respiratory bands significantly improves the ICA analysis. • 3 min SMS-EPI scan provides comparable levels of SNS and TRT as that of a 10 min EPI. Abstract Background Recent advancements in simultaneous multi-slice (SMS) imaging techniques have enabled whole-brain resting-state fMRI (rs-fMRI) scanning at sub-second temporal resolution, providing spectral ranges much wider than the typically used range of 0.01–0.1 Hz. However, the advantages of this accelerated acquisition for rs-fMRI have not been evaluated. New method In this study, we used SMS Echo Planar Imaging (EPI) to probe whole-brain functional connectivity with a short repetition time (TR = 350 ms) and compared it with standard EPI with a longer TR of 2000 ms. We determined the effect of scan length and investigated the temporal filtration strategies that optimize results based on metrics of signal-noise separation and test-retest reliability using both seed-based and independent component analysis (ICA). Results We found that use of either the entire frequency range of 0.01–1.4 Hz or the entire frequency range with the exclusion of typical cardiac and respiratory frequency values tended to provide the best functional connectivity maps. Comparison with existing methods We found that the SMS-acquired rs-fMRI scans had improved the signal-noise separation, while preserving the same level of test-retest reliability compared to conventional EPI, and enabled the detection of reliable functional connectivity networks with scan times as short as 3 min. Conclusions Our findings suggest that whole-brain rs-fMRI studies may benefit from the increased temporal resolution enabled by the SMS-EPI acquisition, leading to drastic scan time reductions, which in turn should enable the more widespread use of rs-fMRI in clinical research protocols. [ABSTRACT FROM AUTHOR]

The article discusses various reports published within the issue, including one on the demonstration of lowering cell culture by Y. Yoshida, K. Takahashi, K. Okita, T. Ichisaka and S. Yamanaka.

The article emphasizes the ability of new nonlinear resistive materials to be tuned for specific applications, which opens up new possibilities in designing electric field control of products for medium and high voltage applications. [ABSTRACT FROM PUBLISHER]

Objectives: The PROGRESS PVL registry evaluated transcatheter aortic valve implantation (TAVI) in patients treated with ACURATE neo, a supra-annular self-expanding bioprosthetic aortic valve.Background: While clinical outcomes with TAVI are comparable with those achieved with surgery, residual aortic regurgitation (AR) and paravalvular leak (PVL) are common complications. The ACURATE neo valve has a pericardial sealing skirt designed to minimize PVL.Methods: The primary endpoint was the rate of total AR over time, as assessed by a core echocardiographic laboratory. The study enrolled 500 patients (mean age: 81.8 ± 5.1 years; 61% female; mean baseline STS score: 6.0 ± 4.5%) from 22 centers in Europe and Canada; 498 patients were treated with ACURATE neo.Results: The rate of ≥ moderate AR was 4.6% at discharge and 3.1% at 12 months; the rate of ≥ moderate PVL was 4.6% at discharge and 2.6% at 12 months. Paired analyses showed significant improvement in overall PVL between discharge and 12 months (P < 0.001); 64.6% of patients had no change in PVL grade, 24.9% improved, and 10.5% worsened. Patients also exhibited significant improvement in transvalvular gradient (P < 0.001) and effective orifice area (P=0.01). The mortality rate was 2.2% at 30 days and 11.3% at 12 months. The permanent pacemaker implantation (PPI) rate was 10.2% at 30 days and 12.2% at 12 months.Conclusions: Results from PROGRESS PVL support the sustained safety and performance of TAVI with the ACURATE neo valve, showing excellent valve hemodynamics, good clinical outcomes, and significant interindividual improvement in PVL from discharge to 12-month follow-up. [ABSTRACT FROM AUTHOR]

Purpose: Synchrotron microbeam radiation therapy (MRT) is an innovative irradiation modality based on spatial fractionation of a high-dose X-ray beam into lattices of microbeams. The increase in lifespan of brain tumor-bearing rats is associated with vascular damage but the physiological consequences of MRT on blood vessels have not been described. In this manuscript, we evaluate the oxygenation changes induced by MRT in an intracerebral 9L gliosarcoma model. Methods: Tissue responses to MRT (two orthogonal arrays (2×400Gy)) were studied using magnetic resonance-based measurements of local blood oxygen saturation (MR_SO2) and quantitative immunohistology of RECA-1, Type-IV collagen and GLUT-1, marker of hypoxia. Results: In tumors, MR_SO2 decreased by a factor of 2 in tumor between day 8 and day 45 after MRT. This correlated with tumor vascular remodeling, i.e. decrease in vessel density, increases in half-vessel distances (×5) and GLUT-1 immunoreactivity. Conversely, MRT did not change normal brain MR_SO2, although vessel inter-distances increased slightly. Conclusion: We provide new evidence for the differential effect of MRT on tumor vasculature, an effect that leads to tumor hypoxia. As hypothesized formerly, the vasculature of the normal brain exposed to MRT remains sufficiently perfused to prevent any hypoxia. [ABSTRACT FROM AUTHOR]

Abstract: Functional MRI (fMRI) brain studies performed in the presence of a steady-state or “blood pool” contrast agent yields activation maps that are weighted for cerebral blood volume (CBV). Previous animal experiments suggest significant contrast-to-noise ratio (CNR) improvements, but these studies have not yet been performed in humans due to the lack of availability of a suitable agent. Here we report the use of the USPIO ferumoxytol (AMAG Pharmaceuticals, Inc., Cambridge, MA) for functional brain activation in humans, termed contrast enhanced functional blood volume imaging (CE-fBVI). Four subjects were scanned during a unilateral finger tapping task with standard blood–oxygen level dependent (BOLD) imaging before contrast and CE-fBVI after contrast injection. The CE-fBVI response showed both a fast (5.8±1.3s) and a slow (75.3±27.5s) component of CBV response to stimuli. A significant CNR gain of approximately 2–3 was found for CE-fBVI compared to BOLD fMRI. Interestingly, less susceptibility-related signal dropouts were observed in the inferior frontal and temporal lobes with CE-fBVI. The combination of higher CNR and better spatial specificity, enabled by CE-fBVI using blood pool USPIO contrast agent opens the door to higher resolution brain mapping. [Copyright &y& Elsevier]

A model of magnetic components is presented which includes saturation and static hysteresis and covers a wide frequency range. A dedicated setup measures the B–H curves for extraction of the model parameters and for model validation. The magnetic model is then represented as a spice circuit and is used in transient system simulations of power converters. Simulations and measurements of core losses and the filter performance of common mode chokes are discussed. [ABSTRACT FROM AUTHOR]

ImUnity is an original 2.5D deep-learning model designed for efficient and flexible MR image harmonization. A VAE-GAN network, coupled with a confusion module and an optional biological preservation module, uses multiple 2D slices taken from different anatomical locations in each subject of the training database, as well as image contrast transformations for its training. It eventually generates 'corrected' MR images that can be used for various multi-center population studies. Using 3 open source databases (ABIDE, OASIS and SRPBS), which contain MR images from multiple acquisition scanner types or vendors and a large range of subjects ages, we show that ImUnity: (1) outperforms state-of-the-art methods in terms of quality of images generated using traveling subjects; (2) removes sites or scanner biases while improving patients classification; (3) harmonizes data coming from new sites or scanners without the need for an additional fine-tuning and (4) allows the selection of multiple MR reconstructed images according to the desired applications. Tested here on T1-weighted images, ImUnity could be used to harmonize other types of medical images. [Display omitted] • We propose a modified VAE-GAN model for versatile T1-MRI domain adaptation. • ImUnity harmonizes multi-site data without the need for traveling subjects. • ImUnity removes site and scanner bias while preserving clinical information. • ImUnity reaches state of the art when harmonizing images from traveling subjects. • ImUnity improves clinical classification of Autism Spectrum Disorders. [ABSTRACT FROM AUTHOR]

The PROMUS Element Plus US Post-Approval Study (PE-Plus PAS) was a prospective, open-label, multicenter, observational study designed to examine outcomes in everyday clinical practice in patients treated with everolimus-eluting, platinum-chromium PROMUS Element Plus stents at 52 centers in the United States. This is the first report of results from this large study. The primary end point of the PE-Plus PAS was 12-month cardiac death or myocardial infarction in the more restricted population of "PLATINUM-like" patients pooled from the PE-Plus PAS, PE-PROVE (PROMUS Element European post-approval study), and PLATINUM Workhorse/Small Vessel trials. Additional clinical end points were tested in the overall PE-Plus PAS patient population. Of the 2,683 patients enrolled in PE-Plus PAS, 70% were men, mean age was 64 years, 33% had diabetes, and 29% were "PLATINUM-like." Among the PLATINUM-like patients, 12-month cardiac death or myocardial infarction was 1.8% (33 of 1,855) with an upper 1-sided 95% confidence interval of 2.3%, which was significantly less than the prespecified performance goal of 3.2% (pnoninferiority <0.001). In the overall PE-Plus population, 12-month target vessel failure (defined as death, MI, or revascularization related to the target vessel) was 6.7% (170 of 2,554), cardiac death was 1.4% (37 of 2,554), MI was 1.1% (28 of 2,554), and ARC-definite/probable stent thrombosis was 0.7% (19 of 2,554). A prespecified secondary end point of 12-month target vessel failure in diabetic patients demonstrated a rate of 4.2% (14 of 332) with an upper 1-sided 95% confidence interval of 6.03%, which was significantly less than the performance goal of 12.6% (pnoninferiority <0.001). In conclusion, in this large registry of unselected patients, coronary artery revascularization with the PROMUS Element Plus everolimus-eluting stent demonstrates favorable results with low 1-year clinical event rates. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the regulation of glucose uptake in cells that participate in atherogenesis by stimuli relevant to this process, to gain mechanistic insight into the origin of the (18)fluorine-labeled 2-deoxy-D-glucose (FdG) uptake signals observed clinically. Background: Patient studies suggest that positron emission tomography (PET) using FdG can detect "active" atherosclerotic plaques, yet the mechanism giving rise to FdG signals remains unknown. Methods: We exposed cells to conditions thought to operate in atheroma and determined rates of glucose uptake. Results: Hypoxia, but not pro-inflammatory cytokines, potently stimulated glucose uptake in human macrophages and foam cells. Statins attenuated this process in vitro, suggesting that these agents have a direct effect on human macrophages. Immunohistochemical study of human plaques revealed abundant expression of proteins regulating glucose utilization, predominantly in macrophage-rich regions of the plaques-regions previously proved hypoxic. Smooth-muscle cells and endothelial cells markedly increased rates of glucose uptake when exposed to pro-inflammatory cytokines. Conclusions: Glucose uptake and, probably, FdG uptake signals in atheroma may reflect hypoxia-stimulated macrophages rather than mere inflammatory burden. Cytokine-activated smooth-muscle cells also may contribute to the FdG signal. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the regulation of glucose uptake in cells that participate in atherogenesis by stimuli relevant to this process, to gain mechanistic insight into the origin of the 18fluorine-labeled 2-deoxy-D-glucose (FdG) uptake signals observed clinically. Background: Patient studies suggest that positron emission tomography (PET) using FdG can detect “active” atherosclerotic plaques, yet the mechanism giving rise to FdG signals remains unknown. Methods: We exposed cells to conditions thought to operate in atheroma and determined rates of glucose uptake. Results: Hypoxia, but not pro-inflammatory cytokines, potently stimulated glucose uptake in human macrophages and foam cells. Statins attenuated this process in vitro, suggesting that these agents have a direct effect on human macrophages. Immunohistochemical study of human plaques revealed abundant expression of proteins regulating glucose utilization, predominantly in macrophage-rich regions of the plaques—regions previously proved hypoxic. Smooth-muscle cells and endothelial cells markedly increased rates of glucose uptake when exposed to pro-inflammatory cytokines. Conclusions: Glucose uptake and, probably, FdG uptake signals in atheroma may reflect hypoxia-stimulated macrophages rather than mere inflammatory burden. Cytokine-activated smooth-muscle cells also may contribute to the FdG signal. [ABSTRACT FROM AUTHOR]